The objective of this project is to clarify the nature of cellular molecules responsible for converting a normal cell to its malignant form. Two approaches have been taken. One is to study the nature of heat-sensitive (hs) or cold-sensitive (cs) mutants of Chinese hamster lung cells affected in the expression of the transformed state. Studies of hybridization between the hs mutants, cs mutants, and wild-type cells indicated that there is a complementation in the expression of the transformed state between hs mutants or cs mutants and that the expression of the transformed state is dominant in all hybrid cells. Another approach is to identify the gene product unique for the transformed human cells and examine the relationship between the expression of the specific gene and the transformed state. A unique form of action protein was found in the human fibroblast transformed by 4-nitroquinoline-1-oxide.